The central hypothesis of this reseach is that emphysema is a disease produced by the degradation of lung elastin, an important connective tissue. The elastin is degraded by elastolytic enzymes which are found in circulating neutrophils or alveolar macrophages. This research will study the mechanisms by which the neutrophils enter the lung, how and where they release their elastase and quantitation of degradation peptides of elastin measured in the serum of experimental animals and humans with emphysema to determine whether this is a useful biochemical marker for early disease or prognosis. An experimental model of alpha-1-antitrypsin deficiency has been created by the administration of Chloramine-T. The animals develop patchy emphysema and demonstrate a markedly reduced serum elastase inhibitory capacity. The role of bronchial inhibitors and the mechanism by which alpha-1-antitrypsin inactivates elastase are also under investigation. Dogs are being exposed to long term cigarette smoking to determine if there are ultrastructural changes in the lungs. The role of the factors which control the synthesis of elastin are being investigated. Immunologic methods are being used to identify elastin at the ultrastructural level, determining the site of elastin production and factors which stimulate it.